This is an application for a Mentored Research Scientist Development Award (K01). The goal of the proposed project is to provide the Applicant with the advanced skills needed to establish an independent program of research in cognitive aging using an integrative multi-modal neuroimaging approach to understanding age-related cognitive changes. The Applicant proposes a comprehensive training plan which combines didactic instruction with established researchers; formal coursework; participation in ongoing seminars at Columbia University; conduction of a prospective study and applied training experiences with individual advisors. Specific training goals include acquiring advanced knowledge and skill in the neurobiological mechanisms of cognitive aging: how aging impacts performance on cognitive tests of working memory and measures of cognition such as memory, processing speed and fluid ability. The training plan will be executed in coordination with an ongoing NIA-supported imaging study of cognition, learning and memory in aging (5R01AG026158) whose main goal is to explore changes in functional network recruitment when performance is challenged by task difficulty manipulation. This study does not address how underlying structural and resting blood flow patterns influence age-group functional or cognitive differences. Consequently, the study I am proposing will investigate the interrelations between age-related gray matter volume, resting cerebral blood flow, and functional activity. The goal of this study will be to assess whether resting blood flow and gray matter volume are independent or concomitant predictors of functional reorganization and to determine how changes in these measures mediate the relationship between age and cognition. The proposed project aims will therefore elucidate the interrelationships between multiple measures of neurobiological changes associated with aging and will serve as a bridge for the Applicant to establish an independent investigator career in conducting multi-modal neuroimaging studies in aging populations. PUBLIC HEALTH RELEVANCE: Currently, many approaches (functional or structural neuroimaging, behavioral or neuropsychological testing) to aging research are performed independently thus diminishing their impact on understanding the overall effects of normal aging on the brain. The current research proposal integrates measures of neural activity (functional activations) and underlying brain structure (cerebral blood flow and brain tissue volume) to study their influences on the relationship between advancing age and decreased performance on cognitive tests.